CMOS-Integrated Fluorescence Biochip Arrays Abstract Array technologies have been responsible for a multitude of discoveries in genomics and proteomics. However, they require sophisticated and highly accurate instrumentation. Today, the bulkiness, cost, and complexity of array readers have become barriers to their adoption in point-of-care (PoC) applications. There is thus a huge demand for rugged, portable, low cost, and ease-of-use systems that can be used outside of core facilities. In this proposal, we will develop a semiconductor-integrated solution for this problem: a CMOS-integrated fluorescence biochip. This system offers the best of both worlds by integrating the gold standard detection modality of biotechnology (fluorescence detection) with commercially available, conventional semiconductor manufacturing processes (complementary metal-oxide-semiconductor, CMOS). The active array substrates include not only the individual transducers required for sensing, but also the low-noise and high dynamic range sensor circuitry and electronic signal analysis blocks. Our preliminary results have demonstrated that by using CMOS, we will not only offer unprecedented detection dynamic range, but also make the cost of the integrated biochip arrays negligible. The latter is a truly unique criterion, as it justifies integration efforts by allowing the biochip array (effectively the reader) to be disposable. In this Phase I project, we plan to design and optimize a biochip system for the widely used DNA microarrays in molecular diagnostics applications with <1000 DNA capturing spots. The integrated biochip will be capable of high performance and multicolor fluorescence detection within the visible-range (=400nm to 800nm) with an array size of 1000 and a pixel pitch of 100 m. The specific tasks in this project will be to (1) design and fabricate the electronics circuits that are required for such CMOS biochips, (2) integrate the emission filter, (3) optimize the surface functionalization protocols, and (4) create a microarray-compatible fluidics module for seamless experimentation. Our ultimate quantitative goal of this Phase I SBIR is to experimentally validate the whole system for DNA microarray applications and further develop and commercialize this technology in Phase II.